Induction of TLR4-dependent CD8+ T cell immunity by murine β-defensin2 fusion protein vaccines

H. J. Park, H. Qin, S. C. Cha, R. Sharma, Y. Chung, K. S. Schluns, S. S. Neelapu, W. W. Overwijk, P. Hwu, L. W. Kwak

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Our laboratory previously described the strategy of fusing chemokine receptor ligands to antigens in order to generate immunogenic DNA vaccines. In the present study, we produced mouse β-2 defensin (mBD2) fusion proteins using both ovalbumin (OVA) and gp100 as model antigens. Superior cross-presentation by dendritic cells (DC) was observed for mBD2 fused antigens over unfused antigens in vitro. In vivo, we observed significant increases in the expansion of adoptively transferred antigen-specific MHC class I, but not class II-restricted T cells after immunization with mBD2 fused antigen over antigen alone. This enhanced expansion of class I restricted T cells was Toll-like receptor 4 (TLR4) dependent, but CC chemokine receptor 6 (CCR6) independent. Superior tumor resistance was observed for mBD2-fusion protein vaccines, compared to unfused antigen, in both B16-OVA and B16 tumor models. These data suggest that production of mBD2 fusion proteins is feasible and that the vaccines facilitate in vivo expansion of adoptively transferred T cells through a TLR4-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)3476-3482
Number of pages7
JournalVaccine
Volume29
Issue number18
DOIs
StatePublished - Apr 18 2011

Keywords

  • Cancer vaccine
  • Defensin beta 2 (mBD2)
  • TLR4

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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